The palladium-catalyzed hydrostannation of terminal arylalkynes was achieved. The regioselectivity of the H-Sn bond addition across the triple bond was found to be controlled by an ortho substituent on the aromatic ring, whatever its electronic nature, to give exclusively alpha-branched vinylstannanes 2 in accordance with Markovnikov's rule. Subsequent Stille cross-coupling reaction of 2 with a variety of aryl halides readily provided, in moderate to good yields, a family of functionalized 1,1-diarylethylenes 1.

A novel class of isocombretastatin A-4 (isoCA-4) analogues with modifications at the 3'-position of the B-ring by replacement with C-linked substituents was studied. Exploration of the structure-activity relationships of theses analogues led to the identification of several compounds that exhibit excellent antiproliferative activities in the nanomolar concentration range against H1299, MDA-MB231, HCT116, and K562 cancer cell lines; they also inhibit tubulin polymerization with potency similar to that of isoCA-4. 1,1-Diarylethylenes 8 and 17, respectively with (E)-propen-3-ol and propyn-3-ol substituents at the 3'-position of the B-ring, proved to be the most active in this series. Both compounds led to the arrest of various cancer cell lines at the G(2) /M phase of the cell cycle and strongly induced apoptosis. Docking of compounds 8 and 17 in the colchicine binding site indicated that their C3' substituents guide the positioning of the B-ring in a manner different from that observed for isoCA-4.

Tuberculosis (TB) remains one of the major causes of death worldwide, in particular because of the emergence of multidrug-resistant TB. Herein we explored the potential of an alternative class of molecules as anti-TB agents. Thus, a series of novel 3-substituted triazolophthalazines was quickly and easily prepared from commercial hydralazine hydrochloride as starting material and were further evaluated for their antimycobacterial activities and cytotoxicities. Four of the synthesized compounds were found to effectively inhibit the Mycobacterium tuberculosis (M.tb) H37 Rv strain with minimum inhibitory concentration (MIC) values <10 μg mL(-1) , whereas no compounds displayed cytotoxicity against HCT116 human cell lines (IC50 >100 μm). More remarkably, the most potent compounds proved to be active to a similar extent against various multidrug-resistant M.tb strains, thus uncovering a mode of action distinct from that of standard antitubercular agents. Overall, their ease of preparation, combined with their attractive antimycobacterial activities, make such triazolophthalazine-based derivatives promising leads for further development.

No abstract

Cinnamic derivatives clearly appear as attractive drug candidates to combat TB. So far, literature has reported that they are easy to synthesize and have promising anti-TB activities. Nevertheless, the mode(s) of action of these small molecules remain(s) to date obscure, which is why the implicated molecular mechanisms deserve to be investigated in further detail in the near future.

Review: 93 refs.

Organo-tin compounds S 4800Palladium-Catalyzed Markovnikov Terminal Arylalkynes Hydrostannation: Application to the Synthesis of 1,1-Diarylethylenes. -Hydrostannation of o-substituted arylalkynes proceeds with excellent regioselectivity yielding α-styryl stannanes exclusively. The reaction of para-, meta-, and unsubstituted arylakynes, however, provides mixtures of olefinic products. Stille coupling of the α-styryl stannanes allows an efficient access to 1,1-diarylethylenes. -(HAMZE, A.; VEAU, D.; PROVOT, O.; BRION, J.-D.; ALAMI*, M.; J. Org. Chem. 74 (2009) 3, 1337-1340; Lab. Chim. Therap., Fac. Pharm., BIOCIS, Univ. Paris-Sud, F-92296 Chatenay-Malabry, Fr.; Eng.) -Jannicke 24-189